Design, synthesis and biological evaluation of 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives as anti-prostate cancer agents

  • Bioorg Med Chem Lett. 2017 Mar 1;27(5):1199-1204. doi: 10.1016/j.bmcl.2017.01.065.
K Saravanan  1 ,  R Elancheran  2 ,  S Divakar  3 ,  S Athavan Alias Anand  1 ,  M Ramanathan  3 ,  Jibon Kotoky  2 ,  N K Lokanath  4 ,  S Kabilan  5
Affiliations
  • 1. Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalai Nagar 608002, Tamil Nadu, India.
  • 2. Drug Discovery Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati 781035, Assam, India.
  • 3. Department of Pharmacology, PSG College of Pharmacy, Coimbatore 641004, Tamil Nadu, India.
  • 4. Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru 570 006, India.
  • 5. Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalai Nagar 608002, Tamil Nadu, India. Electronic address: [email protected].
PMID: 28162857 DOI: 10.1016/j.bmcl.2017.01.065
Abstract

The structural modification and molecular docking-based screening approaches on thiazole-based isoindolinediones were imposed to find the novel 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives. The best fit compounds (6a-n) were synthesized and evaluated their antiproliferative activities on the prostate Cancer cell lines (PC-3 & LNCaP). Among them, the compound, 6m exhibited good activity, particularly on LNCaP (IC50=5.96±1.6μM), moderately active against PC-3 cell lines as compared to bicalutamide. The compound, 6m decreased the androgen-mediated transcription of ARE-mRNA in PSA, TMPRSS2, c-Myc and cyclin D1 than R-bicalutamide. The compounds, 6e and 6f were reconfirmed through single crystal XRD analysis. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. These findings may provide vital information for the development of anti-prostate Cancer agents.

Keywords
AR antagonist; Androgen receptor; Isoindolinediones; Molecular docking; Prostate cancer.